Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane

Takida, Satoshi; Maeda, Yusuke; Kinoshita, Taroh

doi:10.1042/bj20070234

Cited by 93 publications

(87 citation statements)

References 25 publications

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“…While our work was in progress, Takida et al reported that a knockdown of p23 results in delayed plasma membrane appearance of a transfected VSV-G-GPI hybrid molecule and of transfected decay-accelerating factor, a GPI-anchored protein (Takida et al, 2008). This work is consistent with our data.…”

Section: Role Of P24 Proteins In Selective Er Export Of Gpianchored Psupporting

confidence: 83%

Selective export of human GPI-anchored proteins from the endoplasmic reticulum

Bonnon

Wendeler

Paccaud

et al. 2010

Journal of Cell Science

137

131

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SummarySelective export of transmembrane proteins from the endoplasmic reticulum (ER) relies on recognition of cytosolic-domain-localized transport signals by the Sec24 subunit of the COPII vesicle coat. Human cells express four Sec24 isoforms, termed Sec24A, Sec24B, Sec24C and Sec24D that are differentially required for selective, signal-mediated ER export of transmembrane proteins. By contrast, luminally exposed glycosylphosphatidylinositol (GPI)-anchored membrane proteins cannot bind directly to Sec24 and must either use membrane-spanning cargo receptors or alternative mechanisms for ER export. Little is known about the mechanism underlying export of GPI-anchored proteins from the ER in higher eukaryotes. Using siRNA-based silencing, we identified that ER-to-Golgi transport of the human GPI-anchored protein CD59 requires Sec24, with preference for the Sec24C and Sec24D isoforms, and the recycling transmembrane protein complex p24-p23 that exhibited the same Sec24C-Sec24D isoform preference for ER export. Coimmunoprecipitation indicated unprecedented physical interaction of CD59 as well as a GFP-folate-receptor-GPI-anchor hybrid with a p24-p23 complex. Density gradient centrifugation revealed co-partitioning of CD59 and p24-p23 into biosynthetically early lipid raft fractions, and CD59 transport to the Golgi was cholesterol dependent. The results suggest that the 24p-23p complex acts as a cargo receptor for GPI-anchored proteins by facilitating their export from the ER in a Sec24-isoform-selective manner involving lipid rafts as early sorting platforms.

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Section: Role Of P24 Proteins In Selective Er Export Of Gpianchored Psupporting

confidence: 83%

Selective export of human GPI-anchored proteins from the endoplasmic reticulum

Bonnon

Wendeler

Paccaud

et al. 2010

Journal of Cell Science

137

131

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“…Because of this abnormal glycan structure, we speculate that PIG-O defi cient cells might have a defect in sorting of free or protein anchored GPIs into ER exit sites. The ER exit of GPI-anchored proteins is controlled by glycan remodeling and p24 complexes act as cargo receptors for GPI anchor sorting into COPII vesicles ( 6,39,49 ). In agreement with this model, we observed a global increase in HexCer levels in the remodeling mutants PGAP1 and PGAP5 as well as for the p24 family proteins.…”

Section: Cholesterol Ester Levels Are Reduced In Cells That Do Not Sysupporting

confidence: 76%

“…In contrast to the observed changes in HexCer and ceramide, total sphingomyelin levels were not affected in the proteins associate with p24 family proteins ( 6,39 ). We therefore analyzed the lipid profi le of cells in which the GPI remodeling enzymes PGAP1, PGAP5, or the p24 family members p23 or p24 were silenced respectively.…”

Section: Very Long Chain Sphingomyelin Levels Are Partially Affected mentioning

confidence: 99%

Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels

Loizides‐Mangold

David

Nesatyy

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org anchor has the core structure phosphatidylinositol (PI)-glucosamine (GlcN)-(Mannose) 3 -phosphoethanolamine (EtN-P), which is conserved among all species. After biosynthesis, the GPI anchor is attached posttranslationally to the newly generated C terminus of certain eukaryotic proteins destined for anchoring thereby tethering the protein to the membrane surface by the glycolipid moiety. GPI-anchored proteins can be released from the cell surface by phosphatidylinositol specifi c phospholipases and this cleavage event can induce major conformational changes on the GPIanchored protein itself ( 2 ).At least three organelles, the endoplasmic reticulum (ER), Golgi, and peroxisomes, are involved in the biosynthesis and remodeling of the GPI anchor. The biosynthesis is initiated on the outer side of the ER membrane. After the fi rst two reactions, the GPI anchor precursor is fl ipped and biosynthesis continues on the luminal side of the ER where the diacyl chains of phosphatidylinositol are then replaced by alkyl-acyl chains. This step is impaired in mutants of the peroxisomal alkyl phospholipid biosynthesis pathway ( 3 ).After protein attachment, the GPI anchor undergoes complex remodeling that begins in the ER with the removal of the inositol-linked acyl chain ( 4 ) and the remodeling of the GPI glycan part (5). Glycan remodeling is crucial for sorting GPI-anchored proteins into ER exit sites and their subsequent ER to Golgi transport ( 6 ). In mammalian cells, remodeling of the GPI anchor is then continued in the Golgi where the unsaturated fatty acid of the GPI anchor is replaced by a saturated fatty acid chain ( 7 ). Abstract Glycosylphosphatidylinositol (GPI) anchor biosynthesis takes place in the endoplasmic reticulum (ER).After protein attachment, the GPI anchor is transported to the Golgi where it undergoes fatty acid remodeling. The ER exit of GPI-anchored proteins is controlled by glycan remodeling and p24 complexes act as cargo receptors for GPI anchor sorting into COPII vesicles. In this study, we have characterized the lipid profi le of mammalian cell lines that have a defect in GPI anchor biosynthesis. Depending on which step of GPI anchor biosynthesis the cells were defective, we observed sphingolipid changes predominantly for very long chain monoglycosylated ceramides (HexCer). We found that the structure of the GPI anchor plays an important role in the control of HexCer levels. GPI anchordefi cient cells that generate short truncated GPI anchor intermediates showed a decrease in very long chain HexCer levels. Cells that synthesize GPI anchors but have a defect in GPI anchor remodeling in the ER have a general increase in HexCer levels. GPI-transamidase-defi cient cells that produce no GPI-anchored proteins but generate complete free GPI anchors had unchanged levels of HexCer. In contrast, sphingomyelin levels were mostly unaffected. We therefore propose a model in which the transport of very long chain ceramide from the ER to Golgi is regulated by...

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“…7C). p24 cycles between the ER and Golgi, is a major component of both COPII and COPI vesicles (50), serves as a primer for COPI vesicle formation (51,64), and, in isoform-specific fashion, appears to serve as a cargo receptor for glycosylphosphatidylinositol-anchored proteins (65,66), G-protein coupled receptors (67), and the Wnt ligand wingless (68,69). Proper p24 trafficking and interaction with other binding partners requires hetero-oligomerization among several closely related p24 family isoforms (70 -72).…”

Section: Alg-2/sec31a-prr Interactions Acutely Regulate Cargo Receptomentioning

confidence: 99%

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

Helm

Bentley

Thorsen

et al. 2014

Journal of Biological Chemistry

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Background: Whether ER to Golgi transport requires calcium, the source of calcium, and its mechanism is unknown. Results: A requirement for luminal calcium is demonstrated, and evidence is presented for a molecular effector pathway. Conclusion: Luminal calcium may regulate transport by activating these protein interactions. Significance: The described calcium effector pathway may lead to greater insight into calcium action at multiple transport steps.

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Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane

Cited by 93 publications

References 25 publications

Selective export of human GPI-anchored proteins from the endoplasmic reticulum

Selective export of human GPI-anchored proteins from the endoplasmic reticulum

Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels

Apoptosis-linked Gene-2 (ALG-2)/Sec31 Interactions Regulate Endoplasmic Reticulum (ER)-to-Golgi Transport

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